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Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP. [ABSTRACT FROM AUTHOR]

Purpose: To describe the self-reported practices on the diagnosis, treatment, and follow-up of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by ear, nose, and throat (ENT) specialists in Spain to identify potential areas for management optimization. Methods: A cross-sectional online survey with 16 questions was carried out. Recruitment was performed by emailing registered ENT specialists in the Spanish Society of Otorhinolaryngology and Head and Neck Surgery (SEORL-CCC). Results: In total, 127 ENT specialists completed the survey. Fifty-one percent of respondents combined clinical criteria and objective evidence of mucosal inflammation to diagnose CRSwNP. Patient interview and, to a lower degree, a visual analogue scale were the most employed diagnostic tools to quantify symptom severity. Less than half (45%) routinely used the 22-item sino-nasal outcomes test (SNOT-22) to assess the impact of CRSwNP disease in quality of life. The use of patient-reported outcomes and other clinical evaluation tools showed a larger uptake among ENT specialists that worked at an ENT department with an available rhinology unit. Almost all the specialists surveyed (95%) recommended biological treatment, particularly in patients with uncontrolled CRSwNP with respiratory comorbidities (76%), as well as in candidates for revision surgery (66%). Conclusion: Spanish otorhinolaryngologists showed a trend toward incorporating CRSwNP guideline recommendations in their clinical practice. The observed low uptake of patient-reported outcomes and objective clinical evaluation tools in routine clinical practise have been identified as areas for optimizing the management of patients with CRSwNP. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a highly prevalent condition. CRS is usually managed with intranasal corticosteroids, useful both before as well as after endoscopic sinus surgery (ESS). However, the greatest drawback of these low-volume sprays is the inadequate delivery into the paranasal sinuses, even after ESS. Recent studies have shown that high-volume steroid nasal rinse (HSNR) has a significantly better penetration of the paranasal sinuses. The purpose of this state-of-the-art review is to systematically overview the current literature about the role of nasal rinses with steroids in CRS. Four authors examined four databases (Embase, Pubmed, Scielo, Cochrane). This review identified 23 studies answering 5 research questions. It included 1182 participants, 722 cases, and 460 controls. Available evidence suggests a potential positive effect of HSNR, which seems to be higher in CRS with nasal polyps. More well-designed studies are needed in order to obtain solid conclusions. The evidence is solid regarding the safety of this treatment modality in the short and long-term. We expect that this lack of severe negative effects will facilitate the acceptance of this treatment modality and the development of future studies. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the consistency between the international guidelines recommendations and worldwide standard practices regarding diagnostic work-up and follow-up strategies for managing patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) in the era of monoclonal antibodies. Methods: A questionnaire developed by the Rhinology section of the Young Otolaryngologists of the International Federation of Oto-rhino-laryngological Societies (Yo-IFOS) included items regarding the management of CRSwNP patients, monoclonal prescription, surgical and follow-up procedures, awareness of biologicals availability, and other relevant clinical practices. The online survey was directed to otolaryngologists and distributed in Europe, North America, South America, and the Middle East through otolaryngological and/or rhinological societies. Results: A total of 202 responses were analyzed; the mean participants' age was 45 ± 11 (73% men and 27% women), and 31% were from the United States, Canada 19%, Europe 45%, Middle East and South America 5%. Only 60% of the respondents declared using validated symptoms and endoscopic score systems in their clinical practice. Several practice discrepancies emerged in our cohort, including preferred surgical approach, prescription of preoperative oral steroids, and perioperative antibiotics (59% and 58%, respectively), as well as divergent awareness levels of available biologics for CRSwNP worldwide. Conclusions: CRSwNP needs a complex and time-consuming assessment, according to the latest guidelines. There seems to be a gap between these recommendations and the real-world data, which should draw more attention to bringing them into uniform clinical practice in the near future. [ABSTRACT FROM AUTHOR]

Background: Primary human airway epithelial cells cultured in an air-liquid interface (ALI) develop a well-differentiated epithelium. However, neither characterization of mucociliar differentiation overtime nor the inflammatory function of reconstituted nasal polyp (NP) epithelia have been described. Objectives: 1st) To develop and characterize the mucociliar differentiation overtime of human epithelial cells of chronic rhinosinusitis with nasal polyps (CRSwNP) in ALI culture system; 2nd) To corroborate that 3D in vitro model of NP reconstituted epithelium maintains, compared to control nasal mucosa (NM), an inflammatory function. Methods: Epithelial cells were obtained from 9 NP and 7 control NM, and differentiated in ALI culture for 28 days. Mucociliary differentiation was characterized at different times (0, 7, 14, 21, and 28 days) using ultrastructure analysis by electron microscopy; ΔNp63 (basal stem/progenitor cell), β-tubulin IV (cilia), and MUC5AC (goblet cell) expression by immunocytochemistry; and mucous (MUC5AC, MUC5B) and serous (Lactoferrin) secretion by ELISA. Inflammatory function of ALI cultures (at days 0, 14, and 28) through cytokine (IL-8, IL-1β, IL-6, IL-10, TNF-α, and IL-12p70) and chemokine (RANTES, MIG, MCP-1, IP-10, eotaxin-1, and GM-CSF) production was analysed by CBA (Cytometric Bead Array). Results: In both NP and control NM ALI cultures, pseudostratified epithelium with ciliated, mucus-secreting, and basal cells were observed by electron microscopy at days 14 and 28. Displaying epithelial cell re-differentation, β-tubulin IV and MUC5AC positive cells increased, while ΔNp63 positive cells decreased overtime. No significant differences were found overtime in MUC5AC, MUC5B, and lactoferrin secretions between both ALI cultures. IL-8 and GM-CSF were significantly increased in NP compared to control NM regenerated epithelia. Conclusion: Reconstituted epithelia from human NP epithelial cells cultured in ALI system provides a 3D in vitro model that could be useful both for studying the role of epithelium in CRSwNP while developing new therapeutic strategies, including cell therapy, for CRSwNP. [ABSTRACT FROM AUTHOR]

Keywords: ACE2; chronic rhinosinusitis; COVID-19; eosinophil; olfactory neuroepithelium; SARS-CoV-2; TMPRSS2 EN ACE2 chronic rhinosinusitis COVID-19 eosinophil olfactory neuroepithelium SARS-CoV-2 TMPRSS2 2904 2907 4 09/03/21 20210901 NES 210901 ACKNOWLEDGMENTS This study was partially sponsored by a research grant (FIS PI19/00806) from Instituto Carlos III, Ministerio de Ciencia, Innovación y Universidades, Spain. (G) mRNA expression levels, as revealed by RT-PCR, of genes encoding for SARS-CoV-2 entry protein (ACE2 and TMPRSS2) in olfactory mucosa from CRSwNP patients and control cases. However, ACE2/TMPRSS2 expressions in the ONE from CRSwNP patients, that may be a risk factor for SARS-CoV-2 infection of the olfactory bulbs and brain entry, remain to be investigated. [Extracted from the article]

Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that—potentially severe—side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking. Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease. [ABSTRACT FROM AUTHOR]

Little is known about the long-term effects of either transnasal transsphenoidal endoscopic approach (TTEA) or expanded endonasal approach (EEA). This study assessed the long-term impact of endoscopic skull base surgery on olfaction, sinonasal symptoms, mucociliary clearance time (MCT), and quality of life (QoL). Patients with pituitary adenomas underwent TTEA ( n = 38), while patients with other benign parasellar tumours who underwent an EEA with vascularised septal flap reconstruction ( n = 17) were enrolled in this prospective study between 2009 and 2012. Sinonasal symptoms (Visual Analogue Scale), subjective olfactometry (Barcelona Smell Test-24, BAST-24), MCT (saccharin test), and QoL (short form SF-36, rhinosinusitis outcome measure/RSOM) were evaluated before, and 12 months after, surgery. At baseline, sinonasal symptoms, MCT, BAST-24, and QoL were similar between groups. Twelve months after surgery, both TTEA and EEA groups experienced smell impairment compared to baseline. Moreover, EEA (but not TTEA) patients reported increased posterior nasal discharge and longer MCTs compared to baseline. No significant changes in olfactometry or QoL were detected in either group 12 months after surgery. Over the long-term, expanded skull base surgery, using EEA, produced more sinonasal symptoms (including loss of smell) and longer MCTs than pituitary surgery (TTEA). EEA showed no long-term impact on smell test or QoL. Level of evidence: IIb [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airways frequently associated with asthma. Bacterial infection is a feature of CRSwNP that can aggravate the disease and the response to glucocorticoid treatment. Objective: We examined whether the bacterial product lipopolysaccharide (LPS) reduces glucocorticoid receptor (GR) function in control nasal mucosa (NM) fibroblasts and in nasal polyp (NP) fibroblasts from patients with CRSwNP and asthma. Methods: NP (n = 12) and NM fibroblasts (n = 10) were in vitro pre-incubated with LPS (24 hours) prior to the addition of dexamethasone. Cytokine/chemokine secretion was measured by ELISA and Cytometric Bead Array. GRα, GRβ, mitogen-activated protein-kinase phosphatase-1 (MKP-1) and glucocorticoid-induced leucine zipper (GILZ) expression was measured by RT-PCR and immunoblotting, GRα nuclear translocation by immunocytochemistry, and GRβ localization by immunoblotting. The role of MKP-1 and GILZ on dexamethasone-mediated cytokine inhibition was analyzed by small interfering RNA silencing. Results: Pre-incubation of nasal fibroblasts with LPS enhanced the secretion of IL-6, CXCL8, RANTES, and GM-CSF induced by FBS. FBS-induced CXCL8 secretion was higher in NP than in NM fibroblasts. LPS effects on IL-6 and CXCL8 were mediated via activation of p38α/β MAPK and IKK/NF-κB pathways. Additionally, LPS pre-incubation: 1) reduced dexamethasone’s capacity to inhibit FBS-induced IL-6, CXCL8 and RANTES, 2) reduced dexamethasone-induced GRα nuclear translocation (only in NM fibroblasts), 3) did not alter GRα/GRβ expression, 4) decreased GILZ expression, and 5) did not affect dexamethasone’s capacity to induce MKP-1 and GILZ expression. MKP-1 knockdown reduced dexamethasone’s capacity to suppress FBS-induced CXCL8 release. Conclusion: The bacterial product LPS negatively affects GR function in control NM and NP fibroblasts by interfering with the capacity of the activated receptor to inhibit the production of pro-inflammatory mediators. This study contributes to the understanding of how bacterial infection of the upper airways may limit the efficacy of glucocorticoid treatment. [ABSTRACT FROM AUTHOR]